Enhanced antioxidant and cytotoxic activity of ferrocenyl-substituted curcumin via stabilization of promoter c-MYC silencer element

Abstract

We are reporting a successful attachment of ferrocenyl moiety at the active methylene carbon atom of β-diketone of curcumin via Knoevenagel condensation reaction, to utilize the optimum selectivity toward biological targets. The formation of ferrocenyl curcumin (i.e., Fc-cur) has been confirmed by ¹H NMR, ¹³C NMR, and FT-IR spectra analysis. Further, circular dichroism (CD) spectroscopy, thermal denaturation, absorption, and fluorescence spectroscopy have been used to understand the association of ligand (i.e., Fc-cur) with G-quadruplex. Based on these analysis, the binding mechanism of the ligand i.e., Fc-cur to the parallel and hybrid topology present in different G-quadruplex has been proposed. Further, the binding and modes of the interaction of Fc-cur with Pu27 c-MYC silencer element and H-telo G-quadruplex have unravelled selective and stronger binding via intercalation with the parallel topology of c-MYC G-quadruplex rather than the hybrid topology of H-telo quadruplex. The manifestation of better antioxidant activity of Fc-cur has been demonstrated by showing a stronger radical scavenging capability than pristine curcumin. The cytotoxicity analysis of the proposed ligand i.e., Fc-cur against Vero and HeLa cells have clearly reflected the nontoxicity toward Vero cells and quite effective against the HeLa cells which reduces the cancer cells more effectively than the already reported for curcumin.

Communicated by Ramaswamy H. Sarma

Keywords:

• c-MYC promoter
• ferrocenyl curcumin
• UV-visible
• fluorescence
• binding

Acknowledgments

The authors express gratitude to Director, NIT Patna and Department of Chemistry, NIT Patna, India for providing the instrumental facilities and support. NSJ is thanking CSIR India for financial support (File No.:01(3071)/21/EMR-II). NSJ is thanking SAIF IISER Bhopal for the NMR facility, Department of Chemical Biology IACS Kolkotta for Circular Dichroism facility, CDRI Lucknow for cytotoxicity assay, and Dr S. Dasgupta (Department of Chemistry, NIT Patna) for providing the facility for organic synthesis. NSJ is thankful to Prof. Nand Kishore, Department of Chemistry, I.I.T Bombay for his valuable suggestion in deriving the thermodynamic parameter. NSJ is also thankful to Dr.Shailendra K. Jha (CSIR - National Metallurgical Laboratory, India) for internal reviewing of manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by Council of Scientific and Industrial Research.